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nicotinamide adenine dinucleotide treatment confers resistance to neonatal ischemia and hypoxia:effects on neurobehavioral phenotypes

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Neural Regeneration Research 2024年第12期19卷 2760-2772页

作者： Xiaowen Xu Xinxin Wang Li Zhang Yiming Jin Lili Li Meifang Jin Lianyong Li Hong Ni Division of Brain Science Institute of Pediatric ResearchChildren’s Hospital of Soochow UniversitySuzhouJiangsu ProvinceChina Department of Pediatric Orthopedics Shengjing Hospital of China Medical UniversityShenyangLiaoning ProvinceChina

Neonatal hypoxic-ischemic brain injury is the main cause of hypoxic-ischemic encephalopathy and cerebral ***,there are few effective clinical treatments for neonatal hypoxic-ischemic brain ***,we investigated the neuroprotective and molecular mechanisms of exogenous nicotinamide adenine dinucleotide,which can protect against hypoxic injury in adulthood,in a mouse model of neonatal hypoxic-ischemic brain *** this study,nicotinamide adenine dinucleotide(5 mg/kg)was intraperitoneally administered 30 minutes befo re surgery and every 24 hours *** results showed that nicotinamide adenine dinucleotide treatment improved body weight,brain structure,adenosine triphosphate levels,oxidative damage,neurobehavioral test outcomes,and seizure threshold in experimental *** mass tag proteomics revealed that numerous proteins were altered after nicotinamide adenine dinucleotide treatment in hypoxic-ischemic brain injury *** reaction monitoring and western blotting confirmed changes in the expression levels of proteins including serine(or cysteine)peptidase inhibitor,clade A,member 3N,fibronectin 1,5'-nucleotidase,cytosolic IA,microtubule associated protein 2,and complexin *** analyses showed that nicotinamide adenine dinucleotide ameliorated hypoxic-ischemic injury through inflammation-related signaling pathways(e.g.,nuclear factor-kappa B,mitogen-activated protein kinase,and phosphatidylinositol 3 kinase/protein kinase B).These findings suggest that nicotinamide adenine dinucleotide treatment can improve neurobehavioral phenotypes in hypoxic-ischemic brain injury mice through inflammation-related pathways.

关键词： brain injury cerebral palsy hypoxia hypoxic-ischemic brain injury inflammation neuroprotection nicotinamide adenine dinucleotide neonate nicotinamide adenine dinucleotide proteomics

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The effects of nicotinamide adenine dinucleotide in cardiovascular diseases: Molecular mechanisms, roles and therapeutic potential

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Genes & Diseases 2022年第4期9卷 959-972页

作者： Xiaokai Zhang Yang Zhang Aijun Sun Junbo Ge Department of Cardiology Zhongshan HospitalFudan UniversityShanghai Institute of Cardiovascular DiseasesShanghai 200032PR China Institute of Biomedical Sciences Fudan UniversityShanghai 200032PR China

Recently, cardiovascular diseases (CVDs) were identified as the leading cause of mortality, imposing a heavy burden on health care systems and the social economy. nicotinamide adenine dinucleotide (NAD+), as a pivotal co-substrate for a range of different enzymes, is involved in many signal transduction pathways activated in CVDs. Emerging evidence has shown that NAD+ can exert remediating effects on CVDs by regulating metabolism, maintaining redox homeostasis and modulating the immune response. In fact, NAD+ might delay ageing through sirtuin and non-sirtuin pathways and thus contribute to interventions for age-related diseases such as CVDs. Considering that robust clinical studies of NAD+ are ongoing, we discuss current challenges and the future translational potential of NAD+ based on existing studies and our understanding. Despite some remaining gaps in its clinical application, NAD+ has been shown to have broad prospects and pan-effects, making it a suitable prophylactic drug for CVDs.

关键词： Ageing Cardiovascular disease Metabolism nicotinamide adenine dinucleotide Sirtuin

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OTOTOXIC MODEL OF OXALIPLATIN AND PROTECTION FROM nicotinamide adenine dinucleotide

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Journal of Otology 2013年第1期8卷 63-71页

作者： DING Dalian JIANG Haiyan FU Yong LI Yongqi Richard Salvi Shinichi Someya Masaru Tanokura Center for Hearing and Deafness State University of New York at Buffalo Sixth People’s Hospital Shanghai Oriental Otolaryngology InstituteShanghai Jiao Tong University Xiangya Hospital Central South University Department of Applied Biological Chemistry University of Tokyo The First Officiated Hospital College of MedicineZhejiang University The Third Affiliated Hospital of Sun Yat-Sen University University of Florida

Oxaliplatin, an anticancer drug commonly used to treat colorectal cancer and other tumors, has a number of serious side effects, most notably neuropathy and ototoxicity. To gain insights into its ototoxic profile, oxaliplatin was applied to rat cochlear organ cultures. Consistent with it neurotoxic propensity, oxaliplatin selectively damaged nerve fibers at a very low dose 1 μM. In contrast, the dose required to damage hair cells and spiral ganglion neurons was 50 fold higher (50 μM). Oxailiplatin-induced cochlear lesions initial-ly increased with dose, but unexpectedly decreased at very high doses. This non-linear dose response could be related to depressed oxaliplatin uptake via active transport mechanisms. Previous studies have demon-strated that axonal degeneration involves biologically active processes which can be greatly attenuated by nicotinamide adenine dinucleotide (NAD+). To determine if NAD+would protect spiral ganglion axons and the hair cells from oxaliplatin damage, cochlear cultures were treated with oxaliplatin alone at doses of 10 μM or 50 μM respectively as controls or combined with 20 mM NAD+. Treatment with 10 μM oxaliplatin for 48 hours resulted in minor damage to auditory nerve fibers, but spared cochlear hair cells. However, when cochlear cultures were treated with 10 μM oxaliplatin plus 20 mM NAD+, most auditory nerve fibers were intact. 50 μM oxaliplatin destroyed most of spiral ganglion neurons and cochlear hair cells with apop-totic characteristics of cell fragmentations. However, 50 μM oxaliplatin plus 20 mM NAD+treatment great-ly reduced neuronal degenerations and hair cell missing. The results suggested that NAD+provides signifi-cant protection against oxaliplatin-induced neurotoxicity and ototoxicity, which may be due to its actions of antioxidant, antiapoptosis, and energy supply.

关键词： oxaliplatin apoptosis copper transporter nicotinamide adenine dinucleotide

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Association of Human Whole-blood NAD+Levels with Nabothian Cyst

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Biomedical and Environmental Sciences 2024年第5期37卷 471-478页

作者： XU Ling WANG Yue Xuan WANG Wei FAN Xue CHEN Xue Yu ZHOU Tian Yun LIU Yu He YU Ye YANG Fan JU Zhen Yu ZHOU Yong WANG Deng Liang Clinical Research Institute Shanghai General HospitalShanghai Jiao Tong University School of MedicineShanghai 200080China NHC Key Lab of Reproduction Regulation Shanghai Engineering Research Center of Reproductive Health Drugs and DevicesShanghai Institute for Biomedical and Pharmaceutical TechnologiesShanghai 200237China Department of Applied Statistics Johannes Kepler University LinzLinz 4040Austria Hematology Center Beijing Key Laboratory of Pediatric Hematology OncologyNational Key Discipline of Pediatrics(Capital Medical University)Key Laboratory of Major Diseases in ChildrenMinistry of EducationBeijing Children's HospitalCapital Medical UniversityNational Center for Children's HealthBeijing 100045China Department of Biostatistics School of Public HealthCheeloo College of MedicineShandong UniversityJinan 250012ShandongChina Clinical Medicine School of Basic MedicineShanghai Medical College Fudan UniversityShanghai 200032China Department of Biochemistry and Molecular Biology Hengyang Medical SchoolUniversity of South ChinaHengyang 421001HunanChina Administrative Office Total Quality Management OfficeTotal Quality Management InstituteShanghai General HospitalShanghai Jiao Tong University School of MedicineShanghai 200080China The First Affiliated Hospital of Jinan University Institute of Aging and Regenerative MedicineJinan UniversityJinan 510632GuangzhouChina Department of Scientific Research The First Affiliated Hospital of Huzhou UniversityHuzhou 313000ZhejiangChina Department of Neurosurgery Neurosurgery Research InstituteThe First Affiliated HospitalFujian Medical UniversityFuzhou 350005FujianChina Department of Neurosurgery Binhai Branch of National Regional Medical CenterThe First Affiliated HospitalFujian Medical UniversityFuzhou 350209FujianChina Fujian Provincial Institutes of Brain Disorders and Brain Sciences The First Affiliated HospitalFujian Medical UniversityFuzhou 350005FujianChina Fujian Provincial Clinical Research Center for Neurological

Objective Little is known about the association between whole-blood nicotinamide adenine dinucleotide(NAD^(+))levels and nabothian *** study aimed to assess the association between NAD^(+)levels and nabothian cysts in healthy Chinese *** Multivariate logistic regression analysis was performed to analyze the association between NAD^(+)levels and nabothian *** The mean age was 43.0±11.5 years,and the mean level of NAD^(+)was 31.3±5.3μmol/*** cysts occurred in 184(27.7%)participants,with single and multiple cysts in 100(15.0%)and84(12.6%)participants,*** total nabothian cyst prevalence gradually decreased from37.4%to 21.6%from Q1 to Q4 of NAD^(+)and the prevalence of single and multiple nabothian cysts also decreased across the NAD^(+)*** compared with the highest NAD^(+)quartile(≥34.4μmol/L),the adjusted odds ratios with 95%confidence interval of the NAD^(+)Q1 was 1.89(1.14–3.14)for total nabothian *** risk of total and single nabothian cysts linearly decreased with increasing NAD^(+)levels,while the risk of multiple nabothian cysts decreased more rapidly at NAD^(+)levels of 28.0 to35.0μmol/***:Low NAD^(+)levels were associated with an increased risk of total and multiple nabothian cysts.

关键词： nicotinamide adenine dinucleotide Nabothian cyst Female Risk factor

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Monitoring microenvironment of Hep G2 cell apoptosis using two-photon fluorescence lifetime imaging microscopy

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Journal of Innovative Optical Health Sciences 2022年第3期15卷 36-44页

作者： Kexin Wang Shiyao Tang Shiqi Wang Fangrui Lin Gengjin Zou Junle Qu Liwei Liu Key Laboratory of Optoelectronic Devices and Systems of Guangdong Province&Ministry of Education College of Physics and Optoelectronic Engineering Shenzhen University ShenzhenGuangdong ProvinceP.R.China

Apoptosis is very important for the maintenance of cellular homeostasis and is closely related to the occurrence and treatment of many *** in cells play a crucial role in programmed cell death and redox *** adenine dinucleotide(NAD(P)H)is the primary producer of energy in mitochondria,changing NAD(P)H can directly reflect the physiological state of ***,NAD(P)H can be used to evaluate metabolic *** this paper,we propose a noninvasive detection method that uses two-photon fluorescence lifetime imaging microscopy(TP-FLIM)to characterize apoptosis by observing the binding kinetics of cellular endogenous NAD(P)*** result shows that the average fluorescence lifetime of NAD(P)H and the fluorescence lifetime of protein-bound NAD(P)H will be affected by the changing pH,serum content,and oxygen concentration in the cell culture environment,and by the treatment with reagents such as H2O2 and ***(PTX).This noninvasive detection method realized the dynamic detection of cellular endogenous substances and the assessment of apoptosis.

关键词： Apoptosis nicotinamide adenine dinucleotide two-photon fluorescence lifetime imaging microscopy imaging microenvironment Hep G2

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Accumulation of poly(adenosine diphosphate-ribose)by sustained supply of calcium inducing mitochondrial stress in pancreatic cancer cells

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World Journal of Gastroenterology 2022年第27期28卷 3422-3434页

作者： Keun-Yeong Jeong Jae Jun Sim Minhee Park Hwan Mook Kim Research and Development Metimedi PharmaceuticalsIncheon 22006South Korea

BACKGROUND The biochemical phenomenon defined as poly adenosine diphosphate(ADP)-ribosylation(PARylation)is essential for the progression of pancreatic ***,the excessive accumulation of poly ADP-ribose(PAR)induces apoptosis-inducing factor(AIF)release from mitochondria and energy deprivation resulting in the caspase-independent death of cancer *** To investigate whether sustained calcium supply could induce an anticancer effect on pancreatic cancer by PAR *** Two pancreatic cancer cell lines,AsPC-1 and CFPAC-1 were used for the *** influx and mitochondrial reactive oxygen species(ROS)were observed by fluorescence *** in enzyme levels,as well as PAR accumulation and energy metabolism,were measured using assay ***-dependent cell death was investigated followed by confirming in vivo anticancer effects by sustained calcium *** Mitochondrial ROS levels were elevated with increasing calcium influx into pancreatic cancer ***,excess PAR accumulation,decreased PAR glycohydrolase and ADP-ribosyl hydrolase 3 levels,and energy deprivation were *** vitro and in vivo antitumor effects were confirmed to accompany elevated AIF *** This study visualized the potential anticancer effects of excessive PAR accumulation by sustained calcium supply on pancreatic cancer,however elucidating a clear mode of action remains a challenge,and it should be accompanied by further studies to assess its potential for clinical application.

关键词： Pancreatic cancer Calcium Reactive oxygen species Poly adenosine diphosphate-ribose Poly adenosine diphosphate-ribosylation Poly adenosine diphosphate-ribose polymerase Apoptosis-inducing factor nicotinamide adenine dinucleotide Anticancer effect

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Jujuboside a Improved Energy Metabolism in Senescent H9c2 Cells Injured by Ischemia, Hypoxia, and Reperfusion through the CD38/Silent Mating Type Information Regulation 2 Homolog 3 Signaling Pathway

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World Journal of Traditional Chinese Medicine 2023年第3期9卷 322-329页

作者： Yi-Ran Hu Hui-Yan Qu Jia-Ying Guo Tao Yang Hua Zhou Shuguang Hospital Shanghai University of Traditional Chinese MedicineShanghaiChina Institute of Cardiovascular Disease Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese MedicineShanghaiChina Institute of Cardiovascular Disease Shanghai Institute of Cardiovascular Disease of Integrated Traditional Chinese and Western MedicineShanghaiChina

Objective:This study explored the myocardial protection role of Jujuboside A through an ischemia–hypoxia–reperfusion(IHR)*** and Methods:H9c2 cells were induced by D-galactose(D-gal)and IHR to establish an aging and IHR *** are four groups of experiments:Control,IHR,D-gal+IHR,and D-gal+IHR+Jujuboside *** viability,Adenosine triphosphate(ATP),reactive oxygen species(ROS),nicotinamide adenine dinucleotide(NAD+),nicotinamide adenine dinucleotide hydride(NADH)content,and NAD+/NADH ratio were detected using biochemical *** cytokines level was detected by enzyme-linked immunosorbent *** expression of CD38,Recombinant NLR Family,pyrin domain-containing protein 3(NLRP3),and silent mating type information regulation 2homolog 3(SIRT3)protein was detected by Western ***:Compared to the IHR group,cell viability,ATP content,NAD+content,NAD+/NADH ratio,and SIRT3 protein expression decreased,ROS level and inflammatory cytokines increased,and CD38 and NLRP3 proteins raised in the D-gal+IHR *** to the D-gal+IHR group,cell viability,ATP content,NAD+content,NAD+/NADH ratio,and expression of SIRT3 protein increased,ROS level and inflammatory cytokines level decreased,and expression of the CD38 and NLRP3proteins decreased in the D-gal+IHR+Jujuboside A ***:Jujuboside A inhibited the expression of CD38,improved energy metabolism disorder,and mitochondrial function,and decreased inflammation in D-gal-induced H9c2 cells.

关键词： CD38 D-galactose ischemia hypoxia and reperfusion Jujuboside A nicotinamide adenine dinucleotide

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Sirtuins are not conserved longevity genes

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Life Metabolism 2022年第2期1卷 122-133页

作者： Charles Brenner Department of Diabetes&Cancer Metabolism Beckman Research Institute of City of HopeDuarteCA 91010 USA

It is central to biology that sequence conservation suggests functional *** longevity is an emergent property of selected traits that integrates capacities to perform physical and mental functions after reproductive *** the yeast SIR2 gene was nominated as a longevity gene based on extended replicative longevity of old mother cells,this is not a selected trait:SIR2 is selected against in chronological aging and the direct targets of SIR2 in replicative lifespan are not *** it would be difficult to imagine how a gene that advantages 1 in 5 million yeast cells could have anticipated causes of aging in animals,overexpression of SIR2 homologs was tested in invertebrates for *** artifactual positive results were reported years before they were sorted out and because it was not known that SIR2 functions as a pro-aging gene in yeast chronological aging and in flies subject to amino acid deprivation,a global pursuit of longevity phenotypes was driven by a mixture of framing bias,confirmation bias,and *** articles that propagate these biases are so rampant that few investigators have considered how weak the case ever was for sirtuins as longevity *** that a few positive associations between sirtuins and longevity have been identified after thousands of person-years and billions of dollars of effort,we review the data and suggest rejection of the notions that sirtuins(i)have any specific connection to lifespan in animals and(ii)are primary mediators of the beneficial effects of NAD repletion.

关键词： sirtuins longevity model organism publication bias resveratrol nicotinamide adenine dinucleotide

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Inhibition of CD38/Cyclic ADP-ribose Pathway Protects Rats against Ropivacaine-induced Convulsion

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Chinese Medical Journal 2017年第19期130卷 2354-2360页

作者： Yu Zou Xin He Qian-Yi Peng Qu-Lian Guo Department of Anesthesiology Xiangya Hospital Central South University Changsha Hunan 410008 China Department of Critical Care Medicine Xiangya Hospital Central South University Changsha Hunan 410008 China

Background： The CD38/cyclic ADP-ribose （cADPR） pathway plays a role in various central nervous system diseases and in morphine tolerance, but its role in local anesthetic intoxication is unknown. The aim of this study was to determine the role of the CD38/cADPR pathway in ropivacaine-induced convulsion. Methods： Forty male Sprague-Dawley rats were randomly divided into five groups （n = 8 per group）： sham group, ropivacaine group, ropivacaine＋8-Br-cADPR （5 nmol） group, ropivacaine＋8-Br-cADPR （10 nmol） group, and ropivacaine＋8-Br-cADPR （20 nmol） group （no rats died）. Rats were intracerebroventricularly injected with normal saline or 8-Br-cADPR 30 min before receiving an intraperitoneal injection of ropivacaine. Electroencephalography and convulsion behavior scores were recorded. The hippocampus was harvested from each group and subjected to nicotinamide adenine dinucleotide and cADPR assays, Western blotting analysis, and malondialdehyde （MDA） and superoxide dismutase （SOD） assays. Results： Intraperitoneal injection of ropivacaine （33.8 mg/kg） induced convulsions in rats. CD38 and cADPR levels increased significantly following ropivacaine-induced convulsion （P = 0.031 and 0.020, respectively, compared with the sham group）. Intraventricular injection of 8-Br-cADPR （5, 10, and 20 nmol） significantly prolonged convulsion latency （P = 0.037, 0.034, and 0.000, respectively）, reduced convulsion duration （P = 0.005, 0.005, and 0.005, respectively）, and reduced convulsion behavior scores （P = 0.015, 0.015, and 0.000, respectively）. Intraventricular injection of 8-Br-cADPR （10 nmol） also increased the B-cell lymphoma-2 （Bcl-2）/Bcl-2-associated X protein ratio （P = 0.044） and reduced cleaved Caspase 3/Caspase 3 ratio, inducible nitric oxide synthase, MDAand SOD levels （P = 0.014, 0.044, 0.001, and 0.010, respectively） compared with the ropivacaine group. Conclusions： The CD38/cADPR pathway is activated in ropivacaine-induced convulsion. Inhibiting this pathway alleviates ropiva

关键词： CD38 Convulsion Cyclic ADP-ribose nicotinamide adenine dinucleotide Ropivacaine

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APPLICATIONS OF INTRANASAL LOW INTENSITY LASER THERAPY IN SPORTS MEDICINE

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Journal of Innovative Optical Health Sciences 2010年第1期3卷 1-16页

作者： TIMON CHENG-YI LIU DE-FENG WU ZHI-QIANG GU MIN WU Lab of Laser Sports Medicine College of Life Science South China Normal University GuangzhouGD510006China

Function-specific homeostasis(FSH)has been defined as a negative-feedback response of a biosystem to maintain its interior function-specific conditions so that the function is perfectly *** is no photobiomodulation of intranasal low intensity laser therapy(ILILT)on a function in its FSH,but ILILT could modulate a function far from its *** rehabilitation has been found to be mediated by the ratio of intracellular nicotinamide adenine dinucleotide(NAD+)and its reduced form NADH,NAD+/NADH,and then sirtuin 1(SIRT1).There might be FSH-specific NAD+/NADH(FSN)and SIRT1 activity(FSA).ILILT might enhance NAD+/NADH and SIRT1 activity until they arrive at FSN and FSA,*** NAD+/NADH and SIRT1 activity of related cells of many athletic diseases such as upper respiratory tract infection,asthma,osteoarthritis,exercise-induced muscle damage,wound,traumatic brain injury,and osteoporosis are lower than FSN and FSA,***,there may be therapeutic effects of ILILT on those athletic ***,many phenomena and the ILILT mechanism have been integrated to support the prophylaxis effects of ILILT on the swine-origin influenza A(H1N1).

关键词： Photobiomodulation homeostasis nicotinamide adenine dinucleotide sirtuin 1 sports medicine

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